Spontaneous Downregulation of Antibody/Autoantibody Synthesis in Susceptible Mice upon Chronic Exposure to Mercuric Chloride is not Owing to a General Immunosuppression

Abstract

Administration of mercuric chloride into susceptible rats and mice induces a systemic autoimmune disease, which is characterized by a T-cell-dependent polyclonal B-cell activation, an increase in serum levels of immunoglobulin (Ig)G1 and IgE, production of antibodies of different specificities and development of renal IgG deposits. A peculiar feature of mercury-induced autoimmunity is that the polyclonal B-cell activation spontaneously disappears in spite of continuous injection of mercury. The exact mechanism(s) for autoregulation of mercury-induced autoimmunity is not well understood. In the present study, we analysed the regulation of mercury-induced immune/autoimmune responses in mice and tested whether spontaneous downregulation of these responses is owing to a general immunosuppression. Mercury-susceptible [SJL (H-2 s )] and -resistant [DBA/2 (H-2 d )] mice were injected with mercury for 4, 10, 15 and 17 weeks. Immune/autoimmune responses were monitored in these mice. Thereafter, mercury-injected mice for 17 weeks were further immunized with horse red blood cells (HRBC) to study whether the subsequent humoral immune response to a foreign antigen is suppressed. We found that except for IgG1 anti-nucleolar antibody production and renal IgG1 deposition, other characteristics of mercury-induced autoimmunity were downregulated in SJL (H-2 s ) mice after chronic treatment with mercury. However, these mice did not show any reduction in the number of splenic antibody-secreting cells and/or in serum titres of specific IgM, IgG1 and IgG2a anti-HRBC antibodies in response to HRBC as compared with naõÈ ve mice. Similarly, in mercury-resistant DBA/2 (H-2 d ) mice, chronic treatment with mercury did not either suppress specific antibody responses against HRBC. Our findings show that the autoregulation of mercury-induced immune/ autoimmune responses observed after chronic treatment with mercury is not owing to a general immunosuppression.

Exposure to mercuric chloride during the induction phase and after the onset of collagen‐induced arthritis enhances immune/autoimmune responses and exacerbates the disease in DBA/1 mice

“…Although the exact mechanism underlying this effect is unknown, it seems likely that under the inflammatory conditions associated with exposure to mercury and collagen together, mercury acts as an additional adjuvant that preferentially enhances the production of anti‐collagen II IgG2a. This suggestion is supported by findings that mercury exerts adjuvant effects on the specific humoral (IgG) immune responses exhibited by rats immunized with ovalbumin 35 and by mice immunized with horse erythrocytes 36 …”

“…This suggestion is supported by findings that mercury exerts adjuvant effects on the specific humoral (IgG) immune responses exhibited by rats immunized with ovalbumin 35 and by mice immunized with horse erythrocytes. 36 The cytokine profiles associated with both CIA and mercury-induced autoimmunity are complex and heterogeneous and vary with the disease stage. 5,[23][24][25] Our analyses of the splenic production of IFN-c (a characteristic Th1 cytokine) and IL-4 (a prototype Th2 cytokine) revealed that at all time-points tested, the ratio of IFN-c/ IL-4 mRNA is increased in all animals with CIA, but reduced in mice treated with mercury alone, suggesting Figure 8.…”

Review: Environmental exposure to mercury and its toxicopathologic implications for public health

“…A peculiar feature of HgIA is that polyclonal B-cell activation spontaneously disappears despite continuous injection of mercury (Roether et al, 2002). The mechanism or mechanisms are not well clarified for autoregulation of HgIA in susceptible rats and mice.…”

“…HgIA normally has the characteristics mentioned previously, that is, T-cell-dependent polyclonal B-cell activation that culminates in increased serum levels of immunoglobulin (IgG1 and IgE), production of antibodies of different specificities, and development of renal IgG deposits. In testing for and analyzing the source of the spontaneous downregulation of mercury-induced immune/autoimmune responses, it has been found that the inhibition of HgIA is not a result of general immunosuppression because the experimental animals were still capable of responding to different or unrelated antigens (Roether et al, 2002).…”

Immunological effects of mercury (IUPAC Technical Report)

“…Even when mercury treatment is continued, the B-cell activation and the titers of autoantibodies decrease thereafter. This seems not to be due to an immunosuppression [63].…”